Our long-term goal is to translate the use of novel, diagnostic plasma biomarkers for alcohol intake developed in non-human primates into a convenient clinical diagnostic tool for human samples. The specific objective of this proposal is to reproduce the differentiation between drinking and naove phenotypes that we have previously demonstrated in non-human primates with the more clinically practical, high throughput multiple reaction monitoring (MRM) technology, and to then translate the use of this technology into the clinical realm with human samples. The central hypothesis is that our diagnostic panel of plasma biomarkers will be able to differentiate drinking versus naove status in human samples via MRM with high sensitivity, specificity, and reproducibility. We base this hypothesis, in part, on the high analytical precision and robustness of MRM technology and on our strong preliminary evidence in non-human primates that a panel of plasma proteins can provide nearly 100% specificity and sensitivity in distinguishing between drinking and naove phenotypes. The rationale for the proposed research is that we can use MRM quantitation, in conjunction with our panel of plasma biomarkers, as a platform to provide objective diagnostic technology that is currently lacking and that would improve our understanding and treatment of excessive alcohol intake.